Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, specific binding sites for luteinizing hormone releasing hormone (LHRH) and its analogues have been demonstrated in biopsy samples of human epithelial ovarian cancer. Their biological significance remained obscure. In this study we ascertained whether such LHRH-binding sites are also present in the human epithelial ovarian cancer cell lines EFO-21 and EFO-27 and if they could mediate antiproliferative effects of LHRH analogues. Using [125I, D-Trp6]LHRH, a high affinity/low capacity binding site was detected in both lines: EFO-21 (Kd1 = 1.5 x 10(-9) M; binding capacity (Bmax1) = 4.9 fmol/10(6) cells) and EFO-27 (Kd1 = 1.7 x 10(-9) M; Bmax1 = 3 fmol/10(6) cells). In addition, a second class of low affinity/high capacity binding sites (EFO-21: Kd2 = 7.5 x 10(-6) M; Bmax2 = 24 pmol/10(6) cells; EFO-27: Kd2 = 4.3 x 10(-6) M; Bmax2 = 14.5 pmol/10(6) cells) was demonstrated. Specific binding of [125I, D-Trp6]LHRH was displaced with nearly equal efficiency by unlabeled [D-Trp6]LHRH, the LHRH-antagonists SB-75 and Hoe-013, and by native LHRH but not by unrelated peptides such as oxytocin and somatostatin. In the presence of 10(-5) M agonist [D-Trp6]LHRH, the proliferation of both cell lines was significantly reduced to 77% of controls after 24 h and to approx. 60% after 6 days. Lower concentrations (10(-9) M) of the agonist, significantly decreased the proliferation to 87.5% for EFO-21 and 86% for EFO-27 after 6 days. These antiproliferative effects were enhanced by increasing doses of [D-Trp6]LHRH and were maximal at 10(-5) M (EFO-21: 65.5% of control, EFO-27: 68% of control). Similar dose-dependent antiproliferative effects were obtained in EFO-21 line with the LHRH-antagonists SB-75 and Hoe-013, while these analogues had no effects on the proliferation of EFO-27 cells. SB-75 partly antagonized the antiproliferative effect of [D-Trp6]LHRH in a dose dependent way in the EFO-27 line. These data suggest that LHRH analogues can directly inhibit the in vitro proliferation of human ovarian cancer cells. This effect might be mediated through the high affinity LHRH binding sites.
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PMID:High affinity binding and direct antiproliferative effects of LHRH analogues in human ovarian cancer cell lines. 822 83

The neurohypophyseal nonapeptide oxytocin (OT) is involved in many biologic functions and regulation of cell proliferation under both physiologic and neoplastic conditions. In some cases, OT exhibits an oxytocin receptor (OTR)-mediated antiproliferative effect on cancer cells. In this study, we examined the effects of OT on ovarian carcinoma progression in vitro and in vivo. We investigated the inhibitory effects of OT on cell growth, invasion and migration in vitro. Furthermore, we examined the OT effects in vivo ovarian carcinoma model. We demonstrated OTR expressions in the large majority of ovarian carcinoma tissues, and OT inhibited not only proliferation but also migration and invasion in ovarian carcinoma cells in vitro. Furthermore, we examined the mechanisms of the antiinvasive ability of OT. Secretion of matrix metalloproteinase 2 was slightly inhibited by 10(-7) M OT, while treatment with 10(-7) M OT for 24 hr remarkably enhanced the expression of E-cadherin. In addition, our in vivo study showed that intraperitoneal administration of OT resulted in the reduction of intraperitoneal dissemination of ovarian carcinoma cells. Mean tumor burden in the OT-treated group (0.2 +/- 0.11 g) was significantly (p < 0.05) less than that of physiologic saline-treated group (0.5 +/- 0.54 g). This evidence implies that OT may functionally suppress peritoneal dissemination in ovarian carcinoma.
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PMID:Oxytocin inhibits the progression of human ovarian carcinoma cells in vitro and in vivo. 1499 73